The work has two objectives. One is to understand the structural basis of acetylcholine receptor function. The second is to understand the pathological mechanisms involved in the disease, myasthenia gravis, in order to improve detection and therapy. Receptor protein is being purified from electric organs and muscle. The polypeptides composing electric organ receptor are being purified and characterized. Antibodies to purified receptor and its component peptides are being used to test similarities between receptors from various sources. Antibodies are also being used to alter receptor function and metabolism. Experimental autoimmune myasthenia gravis (EAMG) is induced by immunization with purified receptor. The pathological mechanisms resulting in impaired neuromuscular transmission in rats with EAMG are being characterized as a model for human MG. Sera and muscle from patients with MG are being studied in parallel with specimens from the animal model. BIBLIOGRAPHIC REFERENCES: Lindstrom, J. An assay for antibodies to human acetylcholine receptor in serum from patients with myasthenia gravis. Clin. Immunol. Immunopath., 7, 36-43 (1977). Keesey, J., J. Lindstrom, H. Cokely, and C. Herrmann. Anti-acetylcholine receptor antibody in neonatal myasthenia gravis. New Engl. J. Med., 296, 55 (1977).